Cells arrested in the plateau phase in vitro resemble the nondividing G0 compartments described in vivo for stem cells and for cells in the viable, but nondividing fractions of some solid tumors. The reentry kinetics of plateau cells in vitro into the cell cycle mimics the recruitment of in vivo G0 cells back into the dividing compartment. In addition the in vitro plateau phase survival responses to several cancer chemotherapy drugs have been confirmed with G0 cells in vivo, as has the recovery from drug induced damage. Success or failure of cancer chemotherapy depends in part on the interaction of the drugs with specific targets within the tumor cells. If there are several clonagenic cell types within the tumor, or if previous treatment with drugs has altered (mutated) the cells, and if some cells are capable of repairing drug-induced damage, the tumor cells may exhibit a differential response to treatment. Some cells will be killed, others will be sensitive, but survive, and some will be resistant. Many cases of differential drug response between dividing and nondividing cells, and between clones of cells surviving previous drug treatment have been observed in vitro and in vivo. Further studies and progress in determining the causal mechanisms of resistance and sensitivity, and a better understanding of growth control are necessary before more effective drug combination therapy is possible. It is important to identify drugs and mechanisms which influence survival, recovery or repair, sensitivity, and recruitment. The systems employed in our proposed studies should produce considerable predictive data on these cellular responses which may be relevant and valuable in the planning and testing of rational and effective drug protocols for the treatment of cancer.